Extra Virgin Olive Oil (EVOO) and the Alzheimer’s Prevention Connection

Alzheimer’s disease (AD) is the most common cause of dementia in the elderly, accounting for almost 5 million cases in the United States.¹ There are 3 major characteristic pathologies of AD: amyloid-b pathology, tau pathology, and synaptic pathologies which affect the signaling between brain cells. Animal studies within the last 5 years have suggested that compounds from extra virgin olive oil (EVOO), including oleocanthal and oleuropein aglycone (OLE), have the capacity to decrease and possibly prevent these pathologies that lead to AD and its neurodegenerative symptoms.

Physiological Mechanisms for the Development of AD

Two major hallmarks of AD include the presence of amyloid plaques and neurofibrillary tangles in the brain. Amyloid plaques occur when amyloid-b peptides accumulate in regions of the brain and assemble themselves forming insoluble plaques.² This aggregation and deposition results in brain degeneration and the impaired cognition that we often see in AD.³

Secondly, neurofibrillary tangles are found in brain tissue of AD patients in relation to abnormal tau function or “tau pathology.” Tau is a microtubule-associated protein found in the axons of neurons responsible for the assembly and spacing of microtubules.⁴ Tau functions in maintaining function of axon structure and transport, but also by protecting nucleic acids from oxidative stress.⁴

When tau proteins become abnormally hyper-phosphorylated they can accumulate, preventing assembly onto microtubules. This results in insoluble neurofibrillary tangles within these cells.⁵ As a result of tau pathology, we find impaired synaptic plasticity and degeneration.⁴

Interestingly, a study published just this month (August, 2017) by Marciniak et al. demonstrated that tau may also function in insulin signaling within the brain, as patients with AD often exhibit insulin resistance within brain tissue, correlated with impaired memory.⁴ This may relate back to the increased incidence of type 2 diabetes in AD patients as a result of glucose and/or insulin resistance.⁴ In this study, mice with tau deletions were shown to exhibit impaired insulin responses, leading to increased food intake, increased circulating leptin, and therefore, weight gain in the form of increased adipose tissue with glucose intolerance.⁴

The Effect of EVOO Compounds on Tau and Amyloid-b Pathologies

Only about 5% of cases of AD are due to genetic mutations responsible for abnormal amyloid-b elevation. As a result, continued research is directed more at prevention of AD as opposed to treatment.¹ EVOO may be one potential option in the prevention of AD progression.

The Mediterranean diet is recognized as an appropriate and beneficial diet to lower risks of cardiovascular diseases. In general, the diet promotes the consumption of fresh fruits, vegetables, and fish, as well as regular daily consumption of olive oil ranging between 30-50mL per day.^1,5 In addition to its association with a longer life expectancy, populations consuming a Mediterranean diet tend to have lower rates of dementia.¹ One cohort study of 1880 elders in the United States showed a 40% decrease in the incidence of AD in populations consuming a Mediterranean diet.⁶

What sets this diet apart from many others, especially the standard American diet, is the chronic daily consumption of olive oil; Thus, the compounds within olive oil have been under investigation for several years.

OLE is a natural phenol found abundantly in EVOO and has been recognized as a potential protectant against AD, as well as obesity, type 2 diabetes, and non-alcoholic hepatitis.² This may be due to the antioxidant effects of OLE³, as previous studies have demonstrated the ability of EVOO to modify the structure of cell membranes in response to oxidative stress from free-radicals.^1,5

Animal models have shown that EVOO has been beneficial in learning and memory, possibly due to this antioxidant nature.⁵ Meanwhile, multiple other studies published recently have shown that consumption of EVOO may be beneficial in protecting against or in slowing the progression of AD.

The mechanisms by which it protects include:

Reduction in amyloid-b production⁵
Enhanced clearance of amyloid-b across the blood-brain barrier (BBB)⁶
Reduction in parenchymal and vascular deposits of amyloid-b^3,5, and
A decrease in tau phosphorylation^1,3

Each of these pathways may provide protection against AD in humans, however, human cognitive function tests with daily and long-term EVOO consumption still needs to be confirmed in clinical studies.

Animal Study of Daily Consumption of EVOO

In an animal study by Qosa et al. daily consumption of EVOO was used to study changes in amyloid-b pathologies in 2 groups of transgenic mice.⁵ Treatment groups consisted of those that were started on EVOO at the early age of 1-month, before pathogenic accumulation of amyloid-b had occurred, and a second treatment group given EVOO at the age of 4-months, after mice had exhibited early onset of amyloid-b pathology. This was to test early prevention and/or delayed onset of disease as well as to assess the ability of EVOO to reverse disease progression.⁵

Results showed that daily consumption of EVOO in both groups led to significantly reduced amyloid-b plaques compared to controls.⁵ Daily consumption for 6 months in the group treated at 1-month of age also showed reduced total tau levels and reduced hyper-phosphorylation.⁵

In a different study, Abuznait et al. found that compound oleocanthal inhibits the formation of neurofibrillary tangles by inhibiting tau fibrillation and aggregation in vitro.⁶ This same compound was shown to protect neurons from the effects associated with amyloid-b aggregation and plaque formation.⁶ One of the ways in which it does this is by inducing specific transporter proteins at the BBB to clear away amyloid-b. We see a progressive decline in the levels of these transport proteins as a part of natural aging, but more so an improper clearance of amyloid-b in AD.⁶

Upon assessing mental function and behaviours, the mice in Qosa et al.’s study displayed significantly improved cognition as measured by burrowing and nest construction behaviours at 7 months when compared to untreated mice.⁵ This was accentuated when compared to the untreated control group of the same age.⁵ Therefore, oleocanthal from EVOO may reduce the risk of AD or related dementias.⁶

Benefits of EVOO in 3 Major Aspects of AD

EVOO contains almost 40 phenolic compounds including oleocanthal and oleuropein aglycone that have shown benefit against amyloid-b and tau pathologies as discussed above.⁵

A study published in June of this year by Lauretti et al. used a triple transgenic model, treating mice that had developed 3 major characteristics of AD: memory impairment, amyloid-b plaques, and neurofibrillary tangles.¹ Their results show promising applications of the chronic consumption of EVOO by positively affecting all three aspects of AD.

Mice treated with daily EVOO consumption showed improvements in memory and spacial learning, in addition to a significant decrease in amyloid-b deposition, and a decrease in tau pathology.¹ This could influence an entire spectrum of AD and its corresponding cognitive decline. This presents a viable therapeutic option for the prevention of AD during aging, as well as a potential to impede current progression of AD.¹

Conclusion

Although much of the current research has used animal models, evidence is mounting that EVOO has protective effects against multiple traits of AD. Two compounds found in EVOO, OLE and oleocanthal, have been identified as modifiers of amyloid-b aggregation, amyloid-b clearance, and tau pathologies. Evidence is currently building that EVOO may also improve memory and learning; however, clinical trials of memory impairment in humans remains to be tested.

References:

Lauretti, E., Iuliano, L., Practicò, D. “Extra virgin olive oil ameliorates cognition and neuropathology of the 3xTg mice: role of autophagy” (2017) Ann Clin and Transl Neurol. 4: 564-574
Casamenti, F., Grossi, C., Rigacci, S., et al. “Oleuropein aglycone: A possible drug against degenerative conditions. In vivo evidence of its effectiveness against Alzheimer’s disease” (2015) J Alzheimers Dis. 45(3): 679-88
Martorell, M., Forman, K., Castro, N., et al. “Potential therapeutic effects of oleuropein aglycone in alzheimer’s disease” (2016) Curr Pharm Biotechnol. 17(11):994-1001
Marciniak, E., Leboucher, A., Caron, E., et al. “Tau deletion promotes brain insulin resistance” (2017) J Exp Med. 214(8): 2257-69
Qosa, H., Mohamed, L.A., Batarseh, Y.S., et al. “Extra-virgin olive oil attenuates amyloid-b and tau pathologies in the brains of TgSwDI mice” (2015) J Nutr Biochem. 26(12): 1479-90
Abuznait, A.H., Qosa, H., Busnena, B.A., et al. “Olive-oil-derived oleocanthal enhances beta-amyloid clearance as a potential neuroprotective mechanism against Alzheimer’s disease: in vitro and in vivo studies” (2013) ACS Chem Neurosci. 4(6): 973-82

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Dr. Sarah King is a licensed Naturopathic Doctor, graduating from the Canadian College of Naturopathic Medicine in 2014. Prior to completing her medical studies, she attended Nipissing University where she received her Honors Bachelor of Science in Biology. Sarah has a passion for women’s health and is a birth doula in Durham and Toronto Region. She treats a wide variety of health conditions including menstrual disorders and hormone balancing, fertility, prenatal care, digestive concerns, skincare and mental health/anxiety. Outside the office Sarah is an avid runner with a love of the GTA’s best forest trails. She also continues to improve her yoga practice and teaches breath work as part of stress management counselling to her patients.

Extra Virgin Olive Oil as Daily Prevention of Alzheimer’s Disease